The PD1/PD-L1 pathway plays a critical role in balancing immunity and host immunopathology. During chronic SIV/HIV infection there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control and its blockade may be a potential immunotherapeutic target.
Lymph node biopsies from HIV infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV infected rhesus macaques (RMs).
PD-L1 expression was observed in cells with myloid/macrophage morphology (M) in HIV infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment.
Administration of anti-PD-L1 in chronic SIV infected RMs was well tolerated. Overall these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans.